Реакция #535682

Уравнение реакции

4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride

triethyl amine

4-methyl-oxazole-5-carbonyl-chloride

→

4-methyl-oxazole-5-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide

Выход 78.0%

Растворители

CH3CN

Условия реакции

Обработка

1. 1
   Другоеa suspension was obtained
2. 2
   ФильтрацияThe reaction mixture was filtered
3. 3
   Промывкаthe solid was rinsed with CH3CN (20 mL), water (2×20 mL) and EtOAc (20 mL)

Методика

To a suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (1.90 g, 5.9 mmol) in CH3CN (25 ml), were added triethyl amine (2.05 mL, 14.7 mmol) and 4-methyl-oxazole-5-carbonyl-chloride (0.85 g, 5.9 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was filtered, and the solid was rinsed with CH3CN (20 mL), water (2×20 mL) and EtOAc (20 mL) to afford 4-methyl-oxazole-5-carboxylic acid [2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-amide as a white solid (1.82 g, 78%): mp, 308-310° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, gradient from 10/90 (CH3CN/H2O) to 95/5(CH3CN/H2O) in 10 minutes: tR=5.49 (98%); 1H NMR (DMSO-d6): δ 2.06-2.10 (m, 1H), 2.38 (s, 3H), 2.59-2.64 (m, 2H), 2.85-2.97 (m, 1H), 4.88 (d, J=5.9 Hz, 2H), 5.17 (dd, J=6, 12 Hz, 1H), 7.70-8.47 (m, 4H), 9.05 (t, J=5.9 Hz, 1H), 11.16 (s, 1H). 13C NMR (DMSO-d6) δ: 12.52, 21.96, 30.92, 37.57, 48.86, 121.91, 127.09, 131.51, 133.01, 134.81, 138.86, 138.89, 140.67, 151.42, 157.96, 166.94, 167.51, 169.82, 172.74. Anal Calcd for C19H16N4O6: C, 57.58; H, 4.07; N, 14.14. Found: C, 57.48; H, 4.04; N, 14.33.

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